Retrokor

Each vial contains Ceftriaxone (as sodium) 1 g.

Pharmacology: Mechanism of Action: Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta- lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.
Pharmacodynamics: Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ceftriaxone results from the inhibition of cell wall synthesis and is mediated through Ceftriaxone binding to penicillin binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.
Pharmacokinetics: The pharmacokinetics of ceftriaxone are largely determined by its concentration-dependent binding to plasma albumin. The plasma free (unbound) fraction of the drug in man is approximately 5% over most of the therapeutic concentration range, increasing to 15% at concentrations of 300mg/l. Owing to the lower albumin content, the proportion of free ceftriaxone in interstitial fluid is correspondingly higher than in plasma.
Plasma concentrations: Mean peak concentrations after bolus intravenous injection are about 120mg/l following a 500mg dose and about 200mg/l following a 1g dose; mean levels of 250mg/l are achieved after infusion of 2g over 30 minutes. Intramuscular injection of 500mg ceftriaxone in 1% Lidocaine Injection BP produces mean peak plasma concentrations of 40-70 mg/l within one hour. Bioavailability after intramuscular injection is 100%.
Excretion: Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine (almost exclusively by glomerular filtration) and the remainder via the biliary and intestinal tracts. The total plasma clearance is 10-22 ml/min. The renal clearance is 5- 12 ml/min. A notable feature of ceftriaxone is its relatively long plasma elimination half-life of approximately eight hours which makes single or once daily dosage of the drug appropriate for most patients. The half-life is not significantly affected by the dose, the route of administration or by repeated administration.
Pharmacokinetics in special clinical situations: In the first week of life, 80% of the dose is excreted in the urine; over the first month, this falls to levels similar to those in the adult. In infants aged less than 8 days the average elimination half-life is usually two to three times longer than that of young adults.
In elderly persons aged over 75 years, the average elimination half-life is usually two to three times longer that in the young adult group. As with all cephalosporins, a decrease in renal function in the elderly may lead to an increase in half-life. Evidence gathered to date with ceftriaxone however, suggests that no modification of the dosage regimen is needed.
In patients with renal or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased; if liver function alone is impaired, renal elimination is increased.
Cerebrospinal fluid: Ceftriaxone crosses non-inflamed and inflamed meninges, attaining concentrations 4-17% of the simultaneous plasma concentration.

Susceptible organisms: Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Pneumococcus, group A streptococcus, group B streptococcus (Streptococcus agalactiae), Streptococcus viridans, Streptococcus bovis, Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Klebsiella spp. (Klebsiella pneumoniae), Moraxella, Proteus morganii, Proteus mirabilis, Proteus vulgaris, Providencia, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Plesimonas shigelloides, Pseudomonas aeruginosa (some strains are resistant), Salmonella spp. (including Salmonella typhi), Serratia spp. (including S. marcescens), Shigella spp., Yersinia spp. (including Y. enterocolitica), Treponema pallidum, Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp. (except Clostridium difficile), Fusobacterium spp. (except F. Mortiferum, F. Varium), Peptococcus spp., Peptostreptococcus spp.
Ceftriaxone is indicated for the treatment of the following infections caused by susceptible microorganisms:
Respiratory infections eg, pneumonia, bronchitis.
Otorhinolaryngology infections, renal or urinary tract infections, meningitidis, perioperative prophylaxis of infections, infections of bone and joint; skin, wound and soft tissue; peritonitis, cholecystitis, cholangitis, gastrointestinal tract, genital infections eg, gonorrhea.
Also for the treatment of infections in patients with decline of immunologic function.

Adults and children >12 years: Usual Dose: 1-2 g, once daily, IV or IM. The total daily dose may increase up to 4 g depending on the type and severity of infection.
Neonates: Usual Dose: 25-50 mg/kg body weight once daily in neonates (within 14 days of age). The total daily dose should not exceed 50 mg/kg body weight.
The dosage in neonates does not have to differentiate between premature and mature babies.
Neonates and children 15 days to 12 years: Usual Dose: 20-80 mg/kg body weight once daily.
Children weighing 50 kg should receive the usual adult dosage of ceftriaxone. In IV administration of >50 mg/kg body weight, Retrokor should be administered for at least 30 min by intermittent IV injection.
Elderly: Usual adult dosage of ceftriaxone should be given.
Meningitis: Initial dose for neonates and children is 100 mg/kg body weight once daily. The total daily dose should not exceed 4 g.
Dosages may be decreased immediately when pathogen and sensitivity of infection or organism are clarified. The following duration of therapy has been shown effective: Neisseria meningitidis, 4 days; Haemophilus influenzae, 6 days; Streptococcus pneumococcus, 7 days.
Gonorrhea: For the treatment of gonorrhea caused by penicillin-susceptible and -resistant organisms, the dose is 250 mg once IM.
Prophylaxis of Perioperative Infections: A single dose of 1-2 g administered 30-90 min before surgery is recommended in order to prevent postoperative infections in surgical operations which was contaminated or have potential to contaminate. In colorectum operation, the administration of Retrokor with 5-nitroimidazole (eg, ornidazole) respectively, separately, simultaneously is effective.
Renal or Hepatic Disorder: If the liver function of the patient with renal disorder is normal, the dosage does not have to be decreased but if the patient is in the terminal stages of kidney failure with 10 mL/min of creatinine clearance, the daily dose should not exceed 2 g.
In patients with hepatic disorder whose renal function is normal, the dosage does not have to be decreased. In the case of severe renal or hepatic failure, serum concentration should be regularly monitored. In dialysis patients, the additional administration after dialysis is not necessary, however, because the excretion rate of dialysis patients may be reduced, serum concentration should be monitored to determine dosage control.
Duration of Therapy: The duration of therapy depends on the type and severity of infection. Generally, therapy should be continued for at least 48-72 hrs after the patient becomes asymptomatic or evidence of the infection has been obtained.
Preparation of Solution: IM Injection: 0.25 and 5 g of Retrokor should be reconstituted in 2 mL of 1% lidocaine HCl; 1 g of Retrokor in 3.5 mL 1% lidocaine HCl. Reconstituted solution should be administered into hips. More than 1 g should not be administered on side of the hips. Pain appears if lidocaine HCl solution is not used in IM. Lidocaine solution should not be administered IV.
IV Injection: 0.25 or 0.5 g of Retrokor should be reconstituted in 5 mL water for injection and 1 g Retrokor in 10 mL water for injection. The reconstituted solution should be slowly injected for 2-4 min IV. Intermittent IV infusion should be continued at least 30 min. 2 g of Retrokor should be dissolved in 40 mL of one of the following solutions not containing calcium: Saline injection; mixture solution of 0.45% sodium chloride and 2.5, 5 or 10% dextrose injection; 5% dextrose injection containing 6% dextran solution, 6-10% hydroxyethyl starch solution or water for injection.
Ceftriaxone solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those mentioned previously due to possible incompatibility. Reconstituted solution is stable for 6 hrs at room temperature or for 24 hrs at 5°C, physically and chemically, however, the solution should be used immediately after preparation. Discard any remaining portion. The color of the solution varies from pale yellow to yellowish brown according to the concentration and storage period.

Patients with history of shock caused by Retrokor. Hypersensitivity to cephalosporins, penicillins or anilide local anesthetic eg, lidocaine.

Prior to administration, susceptibility to Retrokor should be tested to prevent manifestation of resistant bacteria and the duration of treatment should be the minimum needed for the treatment. A patient should be asked about his/her condition in order to predict reaction eg, shock and also his previous skin reaction should be tested.
First aid should be prepared: In case of anaphylactic shock, epinephrine should be injected IV and then glucocorticoid should be administered. After administration, the patient should be observed in the stable state. Regular clinical tests eg, liver, renal, hematologic tests should be performed.
Shadows mistaken for gallstone have been observed in ultrasonography of gall bladder of patients administered with higher than recommended dosage of Retrokor. However, termination of administration cleared the shadows which are precipitates of calcium ceftriaxone. Termination of therapy should be determined by a clinician.
In overdosage, concentrations of Retrokor would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Symptomatic treatment should be performed.
Patients with a history of allergy to drugs.
Patients whose family are susceptible to cause the allergy symptoms eg, bronchial asthma, eruption and urticaria.
Patients with severe renal disorder. Because the plasma concentration is maintained, the drug should be administered by reduced-dose or prolonged administration interval.
Patients who cannot ingest orally or parenteral patients, elderly, patients with poor systemic condition. Patients should be sufficiently observed because avitaminosis K may occur.
Effects on the Ability to Drive or Operate Machinery: There is no report that Retrokor inhibited the patient's driving or operating machinery.
Use in pregnancy & lactation: Since use in pregnancy has not been established, ceftriaxone should be used only when the expected benefits clearly outweigh the potential risks.
Caution should be observed in administration to nursing mothers since a small amount of Retrokor has been distributed in human milk.
Use in children: Safe use in neonates and prematures has not been established. In vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone (Retrokor) should not be administered to hyperbilirubinemic neonates especially prematures.

Since use in pregnancy has not been established, ceftriaxone should be used only when the expected benefits clearly outweigh the potential risks.
Caution should be observed in administration to nursing mothers since a small amount of Retrokor has been distributed in human milk.

Shock: Rarely, shock may occur. If malaise, intra-oral abnormal sense, stridor, dizziness, feeling of defecation, tinnitus or diaphoresis occur, discontinue administration and/or appropriate therapy should be instituted.
Hypersensitivity: If rash, urticaria, erythema, ruber, pruritus, chill, flush, allergic dermatitis, edema, erythema multiforme, anaphylactic or anaphylactoid reactions occur, the administration should be discontinued and/or appropriate therapy should be initiated.
Hematologic: Occasionally, agranulocytosis, eosinophilia, thrombocythemia may occur. Rarely, anemia, hemolytic anemia, thrombocytopenia, prothrombin disorder may occur.
Hepatic: Occasionally, elevations of GOT, GPT, AL-P and the symptom by precipitation of ceftriaxone calcium salt in cholecyst may occur. Rarely, elevations of bilirubin, γ-GTP may occur.
Renal: Rare cases of severe renal disorder including acute kidney failure have been reported. It should therefore be monitored regularly. If any symptoms occur, the administration should be discontinued and/or appropriate therapy should be instituted.
Gastrointestinal: Rarely, severe colitis accompanying with hemofecia of pseudomembranous colitis may occur. If aneilema, frequent diarrhea occur, an appropriate therapy should be instituted or discontinue administration. Occasionally, nausea; vomiting; loose stool, diarrhea or rarely, aneilema, anorexia may also occur.
Respiratory: In the administration of other cephem-series antibiotics, interstitial pneumonia accompanied by flush, cough, dyspnea, abnormal chest X-ray, eosinophilia and PIE syndrome may occur rarely. If the symptoms occur, administration should be discontinued and/or appropriate therapy including the administration of adrenocortical hormone should be instituted.
Superinfection: Rarely, stomatitis, candidiasis may occur.
Avitaminosis: Rarely, avitaminosis K (eg, hypoprothrombinemia, bleeding tendency) and avitaminosis B group (eg, glossitis, stomatitis, anorexia, neuritis) may occur.
Others: Occasionally, headache or edema, precipitation in cholecyst, ventricular extrasystole may occur.

Concomitant administration with similar compounds (other cephem-series compounds) and diuretics eg, furosemide may increase renal impairment.
In vitro studies with gram-negative Bacillus indicates that the antibacterial activity of ceftriaxone and aminoglycosides may be additive or synergistic against some strains of Pseudomonas aeruginosa. This is important in the severe symptoms by pathogens eg, Bacillus procyaneous or in the life-threatening infection. Concomitant administration of both aminoglycosides and ceftriaxone are contraindicated. Both should be administered alone within the recommended dose. There is no evidence that ceftriaxone increases the renal toxicity of aminoglycosides.
A disulfiram-like reaction reportedly occurred in a patient who ingested alcohol while receiving ceftriaxone.
Concomitant administration of probenecid does not appear to affect excretion of ceftriaxone.
Retrokor has no N-methylthiotetrazole side chain relating to intolerance and bleeding against ethanol in the administration of other cephalosporins.
In test tube test, concomitant administration with chloramphenicol resulted to antagonism.
Clinical Tests: Pseudopositive reflex may develop in urinary glucose determination using Benedict's solution, Fehling's solution; Clinitest except Tes-Tape reaction. Positive Coombs' test may occur. Pseudopositive response may develop in the galactosemia test as with other antibiotics.

Pharmaceutical Precautions: A large volume of IV administration may cause rarely angioalgia, thrombophlebitis, flushing, nausea and vomiting. The preparation of injectable solution, sites and methods of injection should be considered with care. Administration should be slow (IV injection).
The reconstituted solution should be used immediately. Use of reconstituted solution in glutathione products and a supplementary solution of amino acids of high concentration.

Store at temperatures not exceeding 30°C. Preserve in hermetic containers.

Cephalosporins

J01DD04 - ceftriaxone ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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